DESCRIPTION: Conflicting reports at the basic science level have polarized the scientific community on the question of whether low level, extremely low frequency electromagnetic fields are capable of significantly affecting cell or tissue behavior at intensity levels corresponding to environmental exposures. The conflicting accounts of extremely low frequency field induced effects may arise, in part, as a result of a basic assumption in most in vitro studies, which is that the principal effect of field exposure is directly at the cellular level. Recent work in our lab has demonstrated that induced, as well as fixed, electric charges at the cell-substrate interface will significantly alter the growth characteristics of anchorage dependent cells. We propose, therefore, that a principal effect of low level EMF exposure is the modification of the physico-chemical characteristics of the cell substrate by the induced electric charge, which subsequently affects the adhesion, growth characteristics and phenotypic expression of anchorage dependent cells. The objective of this four year study is to test the hypothesis that field induced charge at the cell-substrate interface is a principal mechanism by which ELF electric fields modify cell behavior, and to identify how this specific alteration of the substrate interface is transduced to the cell. Preliminary results show that ELF electric field intensities similar to those induced in the adult human by 60 Hz environmental exposures, can influence both tissue adaptation and cell activity. Such fields induce maximum surface charge densities (in vitro) of less than 2 uC/m2, yet in the absence of either a magnetic or electric field, induced positive charge densities of less than 0.6 uC/m2 will significantly affect the growth of anchorage dependent cells. Further we show that induced charge can alter extracellular matrix (ECM) protein adsorption and cell adhesion. Cellular responses to induced charge should therefore depend on the substrate and adsorbed ECM protein characteristics and on the ability of the cell to adapt its adhesion receptor distribution to accommodate the altered adhesion environment. Experiments will be performed to address each of these issues, using an in vitro system in which the intensity of both the fixed and induced electric charge can be accurately controlled. Adsorbed protein, cell adhesion, cell growth, as well as changes in integrin expression, will be assayed.